8/2/10. Sanaz Jalali, Jennifer Demler, Jeremy King. Histoplasmosis is an intracellular mycotic infection of the reticuloendothelial system.

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Histoplasmosis is an intracellular mycotic infection of the reticuloendothelial system. Type of chronic respiratory infection http://www.eregimens.com/regimens/antifungal%20general.

May primarily affect lungs, but may spread to other organs and tissues in the body The spectrum of the disease is wide Samuel Taylor Darling, a pathologist, reported the first case of histoplasmosis

1 Histoplasmosis is an intracellular mycotic infection of the reticuloendothelial system. Type of chronic respiratory infection Sanaz Jalali, Jennifer Demler, Jeremy King It is introduced in the body via the inhalation of conidia of the fungus Histoplasma capsulatum. May primarily affect lungs, but may spread to other organs and tissues in the body The spectrum of the disease is wide Samuel Taylor Darling, a pathologist, reported the first case of histoplasmosis to the Journal of the American Medical Association in Believed it was a protozoan similar to malaria. He named the fungi Histoplasma capsulatum because of its surrounding capsule. Histoplasmosis is caused by the fungus Histoplasma capsulatum (H. capsulatum). Histoplasma capsulatum Taxonomy Kingdom: Fungi Phylum: Ascomycota Subphylum: Ascomycotina Class: Ascomycetes Order: Onygenales Family: Onygenaceae Genus: Ajellomyces (Histoplasma) 1

Then grows into a yeast form at 37 C -Creamy, slow growing, moist yeast-like colonies formed Microscopic features: At 25 C Hyphae are septate and hyaline At 37 C Narrow-based, budding yeast cells are

2 Etiological agent of histoplasmosis. Is an ascomycete that exhibits clinically relevant dimorphism. Macroscopic features: Grows as a mold form first at 25 C -Colonies are slow growing and granular to cottony in appearance. Then grows into a yeast form at 37 C -Creamy, slow growing, moist yeast-like colonies formed Microscopic features: At 25 C Hyphae are septate and hyaline At 37 C Narrow-based, budding yeast cells are formed. There are 3 variances of H. capsulatum -H. capsulatum var. capsulatum -H. capsulatum var. duboisii -H. capsulatum var. farciminosum (Found in horses) The teleomorphic (sexual) state of the 3 variances is called Ajellomyces capsulatus. Is most common type of H. capsulatum. A dimorphic fungus. Soil saprophyte. Commonly infects the lungs where chronic pulmonary disease may occur. Rarely involve the thyroid glands and may be isolated in fungemia. Have small narrow yeast cells

A mycotic infection primarily involving cutaneous, liver, lung lymphatic, subcutaneous, and bony tissues.

Characteristics: -Nodular, ulcerative cutaneous, and osteolytic lesions of the bone that can disseminate or remain localized. http://www.aafp.

Found worldwide in regions known for humidity and moderate temps Var.

3 A mycotic infection primarily involving cutaneous, liver, lung lymphatic, subcutaneous, and bony tissues. A dimorphic fungus Skin and bone are the most frequently invaded sites. Characteristics: -Nodular, ulcerative cutaneous, and osteolytic lesions of the bone that can disseminate or remain localized. The etiologic agent grows as a large yeast within giant cells. Found worldwide in regions known for humidity and moderate temps Var. capsulatum is endemic in North America- Ohio Mississippi River Valleys, Asia, Australia, Africa and South America Var. duboisii is endemic in Africa. Mostly in central Africa Mainly found in soil with bird or bat droppings. The people down there will probably get infected. 3

Occurs in healthy individuals Occurs in immunocompromised/debilitated people Aids and HIV People you have traveled to endemic areas 500,000 new infections each year in U.S.

inoculum/exposure Underlying health of patient Immunity status to organism Causes a chronic respiratory infection in lungs Asymptomatic to disseminated Symptoms similar to tuberculosis Asymptomatic:

4 Occurs in healthy individuals Occurs in immunocompromised/debilitated people Aids and HIV People you have traveled to endemic areas 500,000 new infections each year in U.S. Outdoor activities Atlas of Fungal Infections Acquired from inhalation of microconidia or fragments of mycelia from soil No evidence of being contagious Manifestation depends upon: Size of inoculum/exposure Underlying health of patient Immunity status to organism Causes a chronic respiratory infection in lungs Asymptomatic to disseminated Symptoms similar to tuberculosis Asymptomatic: Low level exposure Usually in healthy individuals Hilar or mediastinal lymphadenopathy with focal or patchy pulmonary infiltrates Lesions may evolve into nodules representing areas of granuloma formation Nodules and lymph nodes undergo calcification Acute Heavy exposure Presents as diffuse pulmonary infiltrates with some degree of respiratory difficulty Symptoms are flu-like Sub acute Similar to acute form Atlas of Fungal Infections 4

Chronic Flu-like symptoms Calcified lung lesions or lymph nodes Leads to gradual progression with destruction of lung tissue Disseminated Occurs before cellular immunity starts PDH (Progressive

5 Chronic Flu-like symptoms Calcified lung lesions or lymph nodes Leads to gradual progression with destruction of lung tissue Disseminated Occurs before cellular immunity starts PDH (Progressive Disseminated Histoplasmosis) If lesions expand, parenchymal necrosis develops usually followed by granuloma formation and encapsulation Atlas of Fungal Infections Thermally Dimorphic Mold to yeast in human tissue Melanin Heat shock protein 60 Alpha (1,3) glucan Alpha (1,3) glucan synthase and alpha (1,4) amylase Calcium Binding Protein YPS3 (Yeast Phase Specific Protein 3) Ability to modify environment PH M Antigen Catalase B H Antigen Secreted beta glucosidases Ability to survive in phago-lysosomes of macrophages With sub acute form Pericarditis and Rheumatologic inflammatory response Induce a neutrophilic inflammatory response Initial reaction is histiocytic Innate cellular response Leads to recovery 5

Inhalation of microconidia Affinity for bones and skin Pulmonary lesion are rare 2 forms present: Localized Disseminated www.yahoo.

progresses Fatal in not promptly treated Similar to Var.

6 Inhalation of microconidia Affinity for bones and skin Pulmonary lesion are rare 2 forms present: Localized Disseminated Localized Regional lymphadenopathy Mucocutaneous ulcers Large subcutaneous abscesses that complicate osteitis and osteomyelitis Any bone can be infected Disseminated Flu-like symptoms Rapidly progresses Fatal in not promptly treated Similar to Var. Capsulatum Dimorphic Melanin Possible for Proteinase and collagenase Breaks down proteinaceous components of host tissue leading to typical necrosis observed in lesions caused by the fungus. For both localized and disseminated form A dispersed granulomatous inflammatory reaction Enormous number of yeast like cells are clustered within the cytoplasm of giant cells. Sample taken form sputum, lung tissue, blood, CSF, or bone marrow is then cultured and incubated. Only positive test result 60% of the time for chronic patients 15% of the time for acute patients Fungus may take from 2 to 12 weeks before the fungus can be identified. 6

Skin tests Serum test can be conducted with blood, urine, and CSF through radioimmunoassay Highly sensitive in disseminated cases Stains Giemsa stain Methenamine silver stain Tested on blood sputum,

php/jom/article/viewfile/4278/3520 XRAYS or CT scans of chest region Observe lungs and or lymph nodes of chest Antifungal drugs Itranconazole, ketoconazole, amphotericin B, avastin, ketoconazole,

7 Skin tests Serum test can be conducted with blood, urine, and CSF through radioimmunoassay Highly sensitive in disseminated cases Stains Giemsa stain Methenamine silver stain Tested on blood sputum, bone marrow, and lymph node aspirates Tests for antigens and antibodies Potentially high rate of false positive results. ASPERGILLUS BLASTOMYCES AND COCCIDIOIDES XRAYS or CT scans of chest region Observe lungs and or lymph nodes of chest Antifungal drugs Itranconazole, ketoconazole, amphotericin B, avastin, ketoconazole, fluconazole, acetaminophen Length vary depending on each case Surgery is not typical Pericardiocentesis or a pericardial window procedure Removes fluid that would otherwise compress the heart Immunosuppressed individuals should avoid high risk areas such as caves, bridges, construction sites, chicken coops large avian gathering places Wear a Part 84 particulate mask 56 year old male Normally healthy Symptoms of fever, cough, respiratory distress, disorientation, hypotension Positive ID with Histoplasma capsulatum in bone marrow aspirate 7

Patient started on Amphotericin B Condition steadily improved until patient developed aspiration pneumonia on day 3 of treatment and died one week later Possible source of entry was a visit to a

8 Patient started on Amphotericin B Condition steadily improved until patient developed aspiration pneumonia on day 3 of treatment and died one week later Possible source of entry was a visit to a Bangladesh chicken farm What allows for the fungal manifestation in otherwise normally healthy individuals? Possible explanation is a defect in the interferon alpha-interleukin-12 pathway Cytokine pathway that is critical in the defense of viruses More research to follow 32 year old male with advanced HIV Multiple face lesions Initial hospital symptoms included fever, extensive oral thrush, multiple mouth ulcers and an enlarged lymph node. Blood culture returned negative results Lymph node biopsy performed Positive Histoplasma capsulatum identified. Given Amphotericin B intravenously for 7 days followed by a twice daily oral dose for 21 days Followed up with oral itraconazole 200mg twice daily Histoplasmosis/ Histoplasmosis/ Histoplasmosis/ environmentalphysiology.html Atlas of Fungal Infections Journal of Chinese Clinical Medicine Microbes and Infection Journal Pathologic Diagnosis of Fungal Infections Infectious Disease journal Histoplasmosis a review article Medical Mycology Journal 8

9 viewfile/5561/ viewfile/4278/ Histoplasmosis 1. Which variance is mostly found in Central Africa? A. H. capsulatum var. duboisii B. H. capsulatum var. capsulatum C. H. capsulatum var. farciminosum D. All of the above 2. Which variance grows small and narrow yeast cells? A. H. capsulatum var. duboisii B. H. capsulatum var. farciminosum C. H. capsulatum var. capsulatum D. All of the above 3. Histoplasmosis capsulatum mainly infects what part of the body? A. Lungs B. Hair C. Nails D. Bones 4. One of the virulence factors for H. Capsulatum is? A. No melanin B. Mold form in human tissue C. Proteinase D. Heat shock protein One possible explanation for disseminated cases of histoplasmosis in otherwise healthy patients can include a dysfunction of the following? A. Alpha/beta transducing pathway B. Interferon alpha/ interleukin-12 pathway C. Beta epoxidase D. Beta-1,6 glucophosphate pathway 9

Lecture 7: Mycoses Caused by Dimorphic Fungi, Part I

BIOL 4849 Medical Mycology Summer 2006 Histoplasmosis Lecture 7: Mycoses Caused by Dimorphic Fungi, Part I u Most common endemic mycotic disease in the United States u Two different varieties (actually